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Severe LH Suppressed Patients After Administration of a GnRH Antagonist (OPTOMALH)

Primary Purpose

Infertility, Female Infertility, Male Infertility

Status
Completed
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Recombinant LH (Luveris)
Sponsored by
Assuta Hospital Systems
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility, Female Infertility, Male Infertility focused on measuring Infertility, IVF, ovarian stimulation, rec LH, GnRH antagonist

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. The patient is eligible for IVF and will be treated according to the Summary of Product Characteristics (SmPC) and routine practice in participating centres.

    2. The patient must be willing and able to comply with the protocol for the duration of the study.

    3. The patient has given written informed consent with the understanding that the consent may be withdrawn by her at any time without prejudice for her future medical care.

    4. Must be hyper-responder to antagonist according definition

Exclusion Criteria:

  1. Ovarian, uterine or mammary cancer.
  2. Tumours of the hypothalamus and pituitary gland.
  3. Uterine myoma requiring treatment.
  4. Ovarian enlargement or cyst of unknown aetiology.
  5. A clinically significant systemic disease.
  6. Abnormal gynaecological bleeding of undetermined origin.
  7. Known allergy or hypersensitivity to human gonadotrophin preparations.
  8. Entered previously into this study or simultaneous participation in another clinical study.
  9. Age > 39 yrs,
  10. BMI > 32 kg/m2,
  11. Patient with no cycles: PCOS or an anovulatory patient. -

Sites / Locations

  • Women Health Center, Maccabi Health Services

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GnRH antagomnist hyper-responders

Arm Description

Those defined as hyper-responders will be given recombinant LH.

Outcomes

Primary Outcome Measures

The primary endpoint will be the proportion of patients who, after receiving Cetrotide after 4 or 5 days of Gonal -F stimulation, are severely down-regulated.
If LH drops more than 50% from its baseline (as measured before Cetrotide) the patient is defined as "Cetrotide hyper-responder"

Secondary Outcome Measures

Full Information

First Posted
October 28, 2010
Last Updated
September 2, 2013
Sponsor
Assuta Hospital Systems
Collaborators
Maccabi Healthcare Services, Israel
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1. Study Identification

Unique Protocol Identification Number
NCT01936077
Brief Title
Severe LH Suppressed Patients After Administration of a GnRH Antagonist
Acronym
OPTOMALH
Official Title
To Define the Individual Need of Exogenous LH During Ovarian Stimulation for Severe LH Suppressed Patients After Administration of a GnRH Antagonist
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assuta Hospital Systems
Collaborators
Maccabi Healthcare Services, Israel

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The ideal stimulation protocol for ovarian stimulation is under constant debate, as we gain more pharmacological control over the patient hormonal milieu. Specifically, the debate focuses around the ideal LH levels. The concept of an "LH window" was suggested. The need for a threshold level of LH is clearly demonstrated in hypogonado-tropic hypogonadism patients, but also in cycling patients receiving high doses of GnRH antagonist. The Ganirelix dose finding study demonstrated very low implantation rates in the high dose groups (1 mg, 2 mg). The stimulation dynamics in these patients were remarkable for very low E2 and LH levels on the day of hCG. In fact, a functional state of hypogonadotropic hypogonadism is achieved, explaining the poor clinical results (1.5% implantation rate under 2 mg Ganirelix). The same protocol was repeated with added Luveris resulting in excellent pregnancy rates. The recommended daily dose of GnRH antagonist is 0.25 mg which on the average provides a protection from premature LH surge, with moderate suppression of LH. Therefore, most patients do not need supplemented LH after the antagonist is initiated. However, there is a subgroup of patients who hyper-respond to the antagonist (in 0.25 mg dose) with a sharp decrease in LH. This explains contradictory findings in the available studies. The basic assumption in the background of this proposal is that there is a wide range of pituitary responses to GnRH antagonist. Obeying a bell-shape curve, most women have an average response, however, some hypo-respond might ovulate prematurely, and others hyper-respond. In the latter cases, pituitary response will behave as if exposed to a higher dose. How to identify an exposure to a presumed higher dose? Below is a figure from the original paper. A close look indicates that the immediate response to all Ganirelix doses are similar in terms of LH drop, however, the big difference lies in the pituitary recovery 24 hours post Ganirelix dose. While small doses allow for a quick recovery to almost pre-treatment LH levels, high doses result in incomplete recovery. Hence, it is reasonable to speculate that the high response to 0.25 mg dose will lead to slow or incomplete recovery of LH levels 24 hours post the initial dose. It is estimated that about 15% of patients are antagonist hyper-responders. Efforts to individualize patient protocol must target this group as candidates for supplemented LH. This estimate is similar to study findings: Huirne et al Human Reproduction 2005, 20: 359.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Female Infertility, Male Infertility
Keywords
Infertility, IVF, ovarian stimulation, rec LH, GnRH antagonist

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GnRH antagomnist hyper-responders
Arm Type
Experimental
Arm Description
Those defined as hyper-responders will be given recombinant LH.
Intervention Type
Drug
Intervention Name(s)
Recombinant LH (Luveris)
Other Intervention Name(s)
Luveris
Intervention Description
150 IU recombinant LH daily.
Primary Outcome Measure Information:
Title
The primary endpoint will be the proportion of patients who, after receiving Cetrotide after 4 or 5 days of Gonal -F stimulation, are severely down-regulated.
Description
If LH drops more than 50% from its baseline (as measured before Cetrotide) the patient is defined as "Cetrotide hyper-responder"
Time Frame
24 hours after first administration of Cetrotide.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. The patient is eligible for IVF and will be treated according to the Summary of Product Characteristics (SmPC) and routine practice in participating centres. 2. The patient must be willing and able to comply with the protocol for the duration of the study. 3. The patient has given written informed consent with the understanding that the consent may be withdrawn by her at any time without prejudice for her future medical care. 4. Must be hyper-responder to antagonist according definition Exclusion Criteria: Ovarian, uterine or mammary cancer. Tumours of the hypothalamus and pituitary gland. Uterine myoma requiring treatment. Ovarian enlargement or cyst of unknown aetiology. A clinically significant systemic disease. Abnormal gynaecological bleeding of undetermined origin. Known allergy or hypersensitivity to human gonadotrophin preparations. Entered previously into this study or simultaneous participation in another clinical study. Age > 39 yrs, BMI > 32 kg/m2, Patient with no cycles: PCOS or an anovulatory patient. -
Facility Information:
Facility Name
Women Health Center, Maccabi Health Services
City
Haifa
Country
Israel

12. IPD Sharing Statement

Citations:
PubMed Identifier
25452708
Citation
Kol S. Individualized Treatment from Theory to Practice: The Private Case of Adding LH during GnRH Antagonist-based Stimulation Protocol. Clin Med Insights Reprod Health. 2014 Oct 14;8:59-64. doi: 10.4137/CMRH.S17788. eCollection 2014.
Results Reference
derived

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Severe LH Suppressed Patients After Administration of a GnRH Antagonist

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